In the pharmaceutical industry, it is important to know the parameters which characterize the tableting properties of powders which are compressed to form tablets used for human and animal consumption. It is desirable to have a method of quantitatively evaluating the tableting characteristics of a powder before it is mixed with other materials so as to permit detection and rejection of lots that, if used, would introduce problems such as capping or excessive friability. Such methods are also useful to assist in formulating new chemical entities. By being able to initially define what tableting indices are critical, and then by being able to experimentally measure such indices based on tablets or compacts formed from test samples, the need for formulation of large samples and the control and predictability of the tableting performance can be much more reliability controlled and achieved.
It is believe that the bonding index of the powder is probably the most important parameter, and it has been determined that the bonding index itself involves two tableting indices, these being referred to as the best and worst case indices. The difference between the best case and worst case boding indices indicates whether the material is viscoelastic. In the final formulation of the powder viscoelastic, it will be sensitive to the rate that the tableting machine is run, that is, to the strain rate. However, viscoelasticity promotes stronger bonding. Thus, qualitative evaluation of the difference between these best and worst case bonding indices is highly desirable.
An evaluation of the bonding index involves application of a compressive force to a surface of a compact (i.e., a blocklike tablet of compressed powder). This involves creation of a partial spherical indentation in the surface of the compact to permit a hardness value to be determined.
To experimentally determine the worst case bonding index, it is typical to use a procedure whereby a steel ball or sphere is bounded off a surface of the compact, whereby the steel ball creates a partial spherical depression in the compact. The steel ball, upon impact against the surface of the compact, imposes a compressive load on the compact, and the mean pressure under the ball is an indication of the shear strength of the compact under compressive load. This permits determination of the worst case bonding index. A desirable pendulum-type impact tester for this purpose is illustrated by U.S. Pat. No. 4,885,933, owned by the Assignee hereof.
To obtain a hardness which corresponds to the best case bonding index, however, requires the use of a procedure which creates a very slow effective strain rate when compressive load is imposed on the compact, such as by means of a sphere. Such an apparatus is disclosed in U.S. Pat. No. 4,957,003, owned by the Assignee hereof.
The determination of the worst case bonding index also involves a determination of a slow strain rate tensile strength measurement of a compact. This is created by slowly imposing a compressive load on the compact as it is held between opposed and relatively movable platens until the compact fails. This permits measurement of the slow strain rate tensile strength of the compact. An apparatus used for this purpose is also illustrated by aforementioned U.S. Pat. No. 4,957,003.
While the apparatus disclosed by aforementioned U.S. Pat. No. 4,957,003 has been successfully utilized to permit more accurate evaluation of the tableting properties of pharmaceutical powders, nevertheless the testing accuracy resulting from use of this known apparatus is less than desired and hence does not always provide the desired degree of accuracy, reliability and repeatability, particularly since such tests may be conducted at numerous different locations at significantly different times. In particular, it has been discovered that the known apparatus, which utilizes continuous rotation of an AC or DC motor as a driving source, cannot be made to perform with the required or desired degree of control both with respect to speed and displacement of the force-producing ram. The inertia of the drive arrangement is such as to effectively prevent precise control over the indentation of the ball into the tablet, and likewise prevents precise measurement of the force/displacement characteristics upon failure of the tablet during the slow strain rate tensile strength measurement test.
Another test which has been used for evaluating the tableting properties of pharmaceutical powders is normally referred to as the shear cell test. In this procedure, a thin layer of powder is positioned between two opposed rough surfaces, the lower defining a bed, and the upper defining a sled which is movable horizontally along the powder layer. The sled is coupled through a flexible tow line and a force transducer to a linear driver, the latter being driven from a conventional continuous-rotation AC or DC motor via a suitable gear drive. The sled has a horizontal towing force applied thereto and, as the layer of powder undergoes a state of consolidation, the force applied to the sled is effective in overcoming the frictional powder force to movably displace the sled along the powder layer. This test is conducted in a repeated manner to generate a strain gauge output which is of a saw tooth pattern which raises as the pressure builds and then drops substantially to zero as the powder shear is exceeded. In this manner values of powder shear or. flow can be determined. However, the known apparatus for conducting this test possesses similar disadvantages in that the driving ram possesses undesirable inertia and coasting due to the overall drive arrangement, and thus carrying out tests in a highly controlled and precise manner while simultaneously recording precise experimental results is generally not achievable.
Accordingly, it is an object of the present invention to provide an improved multifunction apparatus for testing the properties of pharmaceutical powders so as to permit several different tests to be conducted thereon to permit determination of different properties of the pharmaceutical powders, which tests can be conducted with a high degree of accuracy and reliability so that the test results are not subject to errors caused by poor quality or excessive tolerances associated with the testing apparatus or caused by the mechanical structure and/or inertia associated with the drive arrangement.
More specifically, in the improved multifunction testing apparatus of the present invention, there is provided a slidable ram which cooperates with at least three different test assemblies to permit multiple testing functions to be carried out, such as powder flow determination, tensile strength, and slow strain rate hardness (often referred to as quasi-static hardness). This improved multifunction testing apparatus includes a precision microstepping motor which can be controlled to provide for an extremely large number of steps per rotation, which motor in turn is suitably coupled to the ram, as through a precision nut-screw arrangement, to provide for precise control over both the velocity and linearly displacement of the ram. This enables the ram to be moved through precise small increments, which increments occur at an extremely high rate so that the movement of the ram approaches a linear velocity, but at the same time the velocity and ram displacement can be accurately positioned by controlling the rotational steps of the driving motor. Thus, accurate experimental results can be recorded from suitable force transducers which are coupled to the ram when the apparatus is used for conducting various ones of the three described tests.
In a preferred embodiment, the ram has a high-capacity force transducer associated therewith, and an indentation ball or platen is removably couple thereto for cooperation with either a quasi-static hardness test assembly or a tensile strength assembly, which assemblies interchangeably mount on the test apparatus. The ram is also coupled to a second low-force transducer which can be coupled to a sled when a powder flow test is to be conducted. Outputs from the transducer are preferably fed directly to a computer and/or a recording device (such as an oscilloscope). The computer is also suitably programmed to provide for precise control of the stepping motor to control the physical test parameters, such as the velocity and displacement of the ram.
Other objects and purposes of the present invention will be apparent to persons familiar with arrangements of this general type upon reading the following specification and inspecting the accompanying drawings.